thiourea and Brain-Diseases

A series of amidine, thiourea, and guanidine derivatives of 2-amino-6-(trifluoromethoxy)benzothiazole termed 2, 3, and 4, respectively, and structurally related to riluzole, a neuroprotective drug in many animal models of brain disease, have been synthesized. The biological activity of compounds 2a-e, 3a-f, and 4a,b was preliminarily tested by means of an in vitro protocol of ischemia/reperfusion injury. The results demonstrated that 2c and 3a-d significantly attenuated neuronal injury. Selected for testing of their antioxidant properties, compounds 3a-d were shown to be endowed with a direct ROS scavenging activity. Compounds 3b and 3d were also evaluated for their activity on voltage-dependent Na(+) and Ca(2+) currents in neurons from rat piriform cortex. At 50 microM, compound 3b inhibited the transient Na(+) current to a much smaller extent than riluzole, whereas 3d was almost completely ineffective.

Topics: Amidines; Animals; Antioxidants; Benzothiazoles; Brain Diseases; Calcium; Guanidines; Ion Transport; Neurons; Neuroprotective Agents; Rats; Reactive Oxygen Species; Reperfusion Injury; Sodium; Structure-Activity Relationship; Thiourea

Topics: Anatomy; Anesthesia; Anesthesia, Inhalation; Anesthesia, Local; Autoradiography; Barbiturates; Blood-Brain Barrier; Body Temperature; Brain; Brain Diseases; Brain Injuries; Brain Neoplasms; Carbon Isotopes; Central Nervous System; Cerebral Hemorrhage; Embryology; Humans; Infections; Intracranial Embolism and Thrombosis; Models, Biological; Muscles; Permeability; Regional Blood Flow; Sulfur Isotopes; Thiourea